Genes involved in the determination of segmental identity in Drosophila melanogaster have been identified on the basis of genetic interactions with homeotic mutations, mutations already known to affect the process. Mutations in previously-identified homeotic genes have been recovered, as well as mutations in new homeotic genes. Several of the new homeotic genes are being characterized in more detail. The kismet gene, a post-transcriptional regulator of the Antennapedia gene, spans >70 kb of genomic DNA and encodes a family of transcripts (between 8 and 17 kb in length) from at least two alternative promoters. These transcripts appear to encode a family of novel nuclear proteins with a common 200 kD carboxyl-domain. The brahma gene encodes a nuclear protein that is conserved from yeast to man. The brahma protein is involved in transcriptional activation of multiple homeotic genes, and the sequence similarity to nucleotide-dependent helicases suggests a role in altering chromatin structure. Isolation of mutations that interact with brahma has identified four homeodomain-encoding genes and three known transcriptional regulators. One of the known transcriptional regulators has been shown to map within 20 kb of a cloned Drosophila TFIID subunit (or TAF). This suggests that brahma may have a role in mediating interactions between gene-specific enhancer-binding proteins and the basal transcriptional machinery, possibly by affecting chromatin structure.